DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hearing loss, autosomal recessive 125 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHearing loss, autosomal recessive 125 maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for hearing loss, autosomal recessive 125 is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
What the evidence adds up to
The 1978 symposium paper states that hearing loss is a symptom, not a disease, and that specific diagnosis should be sought in all cases with the objective of reversing the loss, but it also acknowledges that definitive therapy is often lacking. A 1995 review describes the research pipeline for genetic hearing loss as moving from family identification through linkage analysis to gene sequencing and finally to gene-based therapy, but notes that at that time each mutation was at a particular spot in the pipeline and clinical applicability was still largely prospective. A 2004 clinical genetic study of 144 patients with nonsyndromic hearing loss established sex distribution, type, degree, symmetry, laterality, progression, aetiology, and inheritance pattern where possible, but did not report any drug treatment.
A 2020 retrospective study of three children from two non-consanguineous families with DFNB7/11 hearing loss caused by biallelic pathogenic variants in the TMC1 gene found that all three had the typical phenotype of prelingual, severe-to-profound hearing loss. After cochlear implantation, the patients showed an excellent functional outcome, with speech perception, nonverbal cognition, and speech performance comparable to those of patients with DFNB1 deafness. The authors state that their results do not support the variable auditory outcome reported elsewhere in the literature, which they suggest may be affected by social and environmental factors and genetic background. No drug treatment was tested or mentioned in any of these abstracts.
What is still missing is any drug therapy for autosomal recessive hearing loss 125. The 2020 study reports only three patients, all treated with a surgical device rather than a drug. No randomised trial of a pharmacological agent exists for this condition. Patient stratification by specific TMC1 variant, age at intervention, and environmental factors remains unaddressed in any controlled study. Funding for drug discovery or repurposing trials in this specific genetic deafness is absent from the published record.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Medical Genetics · 2003 · 249 citations · open access
Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (<i>OTOF</i>) gene
AbstractIt is estimated that about 1 in 500 children are born with a significant hearing loss.1 Non-syndromic recessive hearing loss (NSRHL) represents a major aetiologic factor in childhood hearing loss since it accounts for approximately 40% of all cases.2 Many of these genetic forms of hearing loss are indistinguishable with current clinical methods. Even so, more than 12 recessive genes have been identified primarily from large consanguineous pedigrees (see the Hereditary Hearing Loss Homepage http://www.uia.ac.be/dnalab/hhh for an overview).
By definition, non-syndromic suggests a “simple” phenotype limited to hearing loss with no other associated symptoms. However, hearing is a complex process. Since a hearing defect might occur at any place along the auditory pathway, it would seem reasonable to expect to be able to differentiate types of NSRHL based on the location where the auditory process is disrupted. Indeed, new audiological testing strategies now give insight into the point where such defects have occurred.
Pure tone audiometry has been the standard method used to measure hearing threshold but, since it subjectively tests the overall integrity of the auditory pathway, it gives only limited information about where that pathway is failing. The auditory brainstem response (ABR) is an objective measure of the overall auditory transduction process. The otoacoustic emissions (OAEs) test is another objective measure of the auditory pathway, which detects responses of the outer hair cells (OHCs) to environmental sound.3–6 A good review of auditory tests can be found in Hood.7
Some children have a hearing loss based on pure tone audiometry and ABR, but with normal OAEs. This type of hearing loss has been defined as auditory neuropathy (AN).8 Subjects with AN can have varying degrees of hearing loss with poor speech reception out of proportion to the degree of hearing loss. In contrast …
Symposium on hearing loss ‐ The otolaryngologist's responsibility.: Medical management of hearing loss.
AbstractMillions of Americans suffer hearing loss resulting in immense social and economic consequences. Hearing loss is merely a symptom or sign and the evaluation and management of afflicted individuals requires a thorough knowledge of etiologic factors and understanding of the underlying pathophysiology. Hearing loss is either conductive, sensorineural, or mixed. It may be congenital or delayed in onset, genetic or progressive or stable. Specific diagnosis should be sought in all cases with the objective being reversal of the hearing loss. Often definitive therapy is lacking yet prevention of progression, when possible; recognition of associated disorders, when present; compensation for disability, when applicable; epidemiologic study; genetic and psycho-social counseling; and habilitation and rehabilitation may still be initiated. A vigorous approach to the patient with hearing loss should be championed by the otolaryngologist.
Current Opinion in Otolaryngology & Head & Neck Surgery · 1995 · 2 citations
Modern clinical methods in genetic hearing loss
AbstractClinical methods in cases of genetic hearing loss have been influenced recently by both methodologic advances and specific findings made in the many research laboratories devoted to human genetic investigation. For the clinician, reports from these laboratories seem to suggest significant breakthroughs accompanied by allusions to clinical applicability. This review presents a rationale for the analysis of the many reports related to genetic hearing loss and their attending clinical impact. This rationale is based on a simplified view of the laboratory effort as a pipeline. A disease (mutation) passes through this pipeline on its way from family identification, through linkage analysis (chromosome localization), to gene sequencing and disease mechanism identification, and finally to gene-based therapy. Each stage of the investigation process has its own impact on clinical methods, and each mutation is in a particular spot in the pipeline at present. The pipeline itself is presented in this paper, along with the nature of the clinical impact of each level of laboratory findings.
American Journal of Audiology · 2004 · 1 citations
Clinical Genetic Study of 144 Patients With Nonsyndromic Hearing Loss
AbstractHearing loss constitutes an important category of congenital defects that can be isolated or part of the phenotypic spectrum of several syndromes. A clinical genetic study was performed on a sample of 144 patients with nonsyndromic hearing loss, establishing the sex distribution, type, degree, symmetry, laterality, progression, etiology, and, when possible, inheritance pattern.
Supplementary Material for: Auditory Outcome after Cochlear Implantation in Children with DFNB7/11 Caused by Pathogenic Variants in <b><i>TMC1</i></b> Gene
Abstract<b><i>Introduction:</i></b> Non-syndromic hereditary hearing loss is characterized by extreme genetic heterogeneity. So far, more than 100 pathogenic or likely pathogenic variants in <i>TMC1</i> gene have been reported in patients with autosomal recessive hearing loss (HL) DFNB7/11. The prevailing auditory phenotype of individuals with DFNB7/11 is congenital, profound, bilateral HL, but the functional outcome after cochlear implantation (CI) described in the literature is variable. The objective of this work is to evaluate the auditory outcome after CI in pediatric patients with DFNB7/11, born to non-consanguineous parents. <b><i>Methods:</i></b> A retrospective analysis of genetic and audiological data of DFNB7/11 patients followed up in a single Italian otolaryngology clinic was performed. Cases with biallelic pathogenic variants in <i>TMC1</i> were selected from the cohort of children with non-syndromic hearing loss who had undergone CI and had been molecularly characterized by multigene panel testing. All patients underwent extensive audiological assessment, and the auditory outcome after CI was evaluated. <b><i>Results:</i></b> DFNB7/11 was diagnosed in a total of 3 patients from 2 non-consanguineous families; a novel disease-causing variant in <i>TMC1</i> was detected [c.962G>A p.(Trp321*)]. All the affected children showed the typical DFNB7/11 phenotype characterized by prelingual, severe-to-profound HL. The patients showed an excellent functional outcome after CI; speech perception, nonverbal cognition, and speech performance were comparable to those of patients with DFNB1 deafness. <b><i>Discussion/Conclusion:</i></b> Our results do not support the variable auditory outcome reported in the literature, which may be affected by several social and environmental factors and by the genetic background.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
